The objective of the proposed research is to increase our understanding of graded synaptic transmission (GST) and, in particular, to study GST as it occurs in spiking neurons. The study will be done at two levels. A comparative, descriptive study between identified neurons of two different preparations (stomatogastric ganglion of the spiny lobster and buccal ganglia of Aplysia) will use intracellular recording, including voltage clamp techniques to study the neuron-to-neuron properties of GST. A detailed study of the mechanisms which are responsible for the neuron-to-neuron GST properties will focus on synaptic input-output properties and the effects of neuronal geometry by using the techniques of voltage clamp, cable analysis, cell clamps, and drugs. Special attention will be given to three-cell chains, where neuron A inhibits neuron B which in turn inhibits neuron C, all using GST (similar to the modulatory effects of presynaptic inhibition on spike-evoked synaptic potentials). Such interactions are typical of local neuronal circuits and may occur through the use of serial synaptic arrays (such as mammalian dendro-dendritic synapses). Little is known about GST and less about GST as it occurs in spiking neurons. Many cells involved in local neuronal circuits in the major invertebrate phyla and in mammals (including man) probably use GST as a major method of synaptic communication. This research should be a first step toward understanding how these neurons function.